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5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893823/ https://www.ncbi.nlm.nih.gov/pubmed/31694297 http://dx.doi.org/10.3390/nu11112678 |
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author | Angelino, Donato Carregosa, Diogo Domenech-Coca, Cristina Savi, Monia Figueira, Inês Brindani, Nicoletta Jang, Saebyeol Lakshman, Sukla Molokin, Aleksey Urban, Joseph F. Davis, Cindy D. Brito, Maria Alexandra Kim, Kwang Sik Brighenti, Furio Curti, Claudio Bladé, Cinta del Bas, Josep M. Stilli, Donatella Solano-Aguilar, Gloria I. dos Santos, Claudia Nunes del Rio, Daniele Mena, Pedro |
author_facet | Angelino, Donato Carregosa, Diogo Domenech-Coca, Cristina Savi, Monia Figueira, Inês Brindani, Nicoletta Jang, Saebyeol Lakshman, Sukla Molokin, Aleksey Urban, Joseph F. Davis, Cindy D. Brito, Maria Alexandra Kim, Kwang Sik Brighenti, Furio Curti, Claudio Bladé, Cinta del Bas, Josep M. Stilli, Donatella Solano-Aguilar, Gloria I. dos Santos, Claudia Nunes del Rio, Daniele Mena, Pedro |
author_sort | Angelino, Donato |
collection | PubMed |
description | Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the “gut-brain axis”. |
format | Online Article Text |
id | pubmed-6893823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68938232019-12-23 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models Angelino, Donato Carregosa, Diogo Domenech-Coca, Cristina Savi, Monia Figueira, Inês Brindani, Nicoletta Jang, Saebyeol Lakshman, Sukla Molokin, Aleksey Urban, Joseph F. Davis, Cindy D. Brito, Maria Alexandra Kim, Kwang Sik Brighenti, Furio Curti, Claudio Bladé, Cinta del Bas, Josep M. Stilli, Donatella Solano-Aguilar, Gloria I. dos Santos, Claudia Nunes del Rio, Daniele Mena, Pedro Nutrients Article Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the “gut-brain axis”. MDPI 2019-11-05 /pmc/articles/PMC6893823/ /pubmed/31694297 http://dx.doi.org/10.3390/nu11112678 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Angelino, Donato Carregosa, Diogo Domenech-Coca, Cristina Savi, Monia Figueira, Inês Brindani, Nicoletta Jang, Saebyeol Lakshman, Sukla Molokin, Aleksey Urban, Joseph F. Davis, Cindy D. Brito, Maria Alexandra Kim, Kwang Sik Brighenti, Furio Curti, Claudio Bladé, Cinta del Bas, Josep M. Stilli, Donatella Solano-Aguilar, Gloria I. dos Santos, Claudia Nunes del Rio, Daniele Mena, Pedro 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models |
title | 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models |
title_full | 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models |
title_fullStr | 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models |
title_full_unstemmed | 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models |
title_short | 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models |
title_sort | 5-(hydroxyphenyl)-γ-valerolactone-sulfate, a key microbial metabolite of flavan-3-ols, is able to reach the brain: evidence from different in silico, in vitro and in vivo experimental models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893823/ https://www.ncbi.nlm.nih.gov/pubmed/31694297 http://dx.doi.org/10.3390/nu11112678 |
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